Genetics Chiari I Malformation. Syringomyelia can be associated with Chiari I malformation. The process by which the Chiari I malformation develops is unknown. Ectopia of the cerebellar tonsils (through the foramen magnum at the base of the skull), which is the defining characteristic of the Chiari I malformation, may result because the posterior fossa does not develop normally. In a clinical study of families with multiple members affected by the Chiari I malformation, we are using magnetic resonance imaging of the brain to evaluate for Chiari I malformation and to measure the size of the osseous structures and volume of the posterior fossa. After phenotyping family members as being affected or unaffected by these traits, we collect DNA specimens from them for genotyping. Genotyping and phenotyping have been completed this year and linkage analysis is being performed. Finding a genetic locus for the Chiari I malformation would lead to a better understanding of the etiology of the Chiari I malformation. Treatment of Syringomyelia. A clinical study elucidating the basis of syringomyelia associated with the Chiari I malformation was completed in which the mechanism was shown, paradoxically, to be outside, not inside, the spinal cord. Successful surgery, by a procedure that does not invade the nervous system (craniocervical decompression), eliminated the anatomic cause of the excess pressure waves and resulted in consistent resolution of syringomyelia. The demonstration of this mechanism should result in more effective treatment for this form of syringomyelia. This year we reported a clinical study of the pathophysiology of persistent syringomyelia after craniocervical decompression. In these subjects, we have found that previous surgery failed simply because it did not relieve the obstruction of the cerebrospinal pathways at the foramen magnum. In another clinical study we are studying primary spinal syringomyelia, a type of syringomyelia not associated with Chiari I malformation. A preliminary finding is that obstruction of the spinal subarachnoid space in primary spinal syringomyelia is associated with enlarged cerebrospinal fluid (CSF) pressure waves superior to the obstruction. Successful surgery for primary spinal syringomyelia opens CSF pathways, reduces CSF pressure waves to normal and resolves syringomyelia, as had successful surgery in our studies of Chiari I-type syringomyelia. This association suggests that primary spinal syringomyelia and Chiari I-type syringomyelia arise from a similar mechanism.